The present invention and our copending applications relate generally to devices for the controlled infusion of medications and specifically, to devices for the administration of a precise dose of a drug-containing fluid. The devices have particular applicability in the subcutaneous delivery of insulin to a diabetic patient so that blood glucose levels can be normalized. The devices can also be used, under the supervision of a physician, to administer cancer chemotherapuetics, antibiotics, heparin and many other pharmacological agents.
Insulin is used primarily in the control of the metabolic disturbance of diabetes mellitus when that disease cannot be satisfactorily controlled by diet alone. This hormone is secreted by the cells of the island of Langerhans in the pancreas and regulates the rate at which the body metabilizes carbohydrates. Insulin, in appropriate doses, enables the diabetic to utilize carbohydrates and fats in a comparatively satisfactory manner so that the concentration of sugar in the blood is confined within normal limits; the urine becomes free of sugar and ketone bodies; and diabetic acidosis and coma are prevented.
The hormone is prepared commercially by extraction from beef and pork pancreas. Various insulin preparations, which differ in rapidity of action and duration of effectiveness, are used in the treatment of diabetes mellitus. Regular insulin is effective almost immediately upon injection and reaches its peak of action within two hours. It is used in diabetic emergencies and when diabetes is first diagnosed. Moreover, regular insulin is often mixed with longer acting forms of insulin for subcutaneous injection as part of the long term management of diabetes.
Other types of insulin developed in recent years are formulated to prolong the action of insulin. Protamine zinc insulin (PAI), isophane insulin (NPH), globin zinc insulin and lente insulin are examples of long-acting insulin preparations. All insulin preparations, however, have the same fundamental pharmacologic action.
In protamine zinc, isophane and lente insulin, the active material is present as a milky-white precipitate and not a clear supernatant fluid. To insure that a constant proportion of this precipitate is present in each dose injected, the vial must be rotated and inverted from end to end several times immediately before the withdrawal of each dose. A failure to observe this procedure can lead to a marked irregularity in the effects of individual doses. The vial, however, should not be shaken vigorously or the suspension made to foam. Such frothing is avoided primarily because the air bubbles produced can alter the dosage measured in the syringe.
Lente insulin combines approximately 70 percent of ultralente and 30 percent of semilente insulin. Lente, semilente and ultralente insulin represent the result of the interaction of zinc on insulin under specific chemical conditions so that higher concentrations of the metallic element are made to combine with the insulin present. As indicated, they are supplied in the form of a suspension of minute crystalline particles. Semilente insulin has the smaller particle size and the shorter action, with a duration of effect of approximately twelve to sixteen hours. Ultralente insulin has the larger particle size and a total duration of effect in excess of thirty-six hours. Thus, lente insulin has a time action which is intermediate between semilente and ultralente insulin. In fact, the action of lente insulin is so close to that of isophane insulin that the two can be used interchangeably.
Insulin is measured in units based on bioassay, and is commercially available in varying strengths; for example, U-40, U-80 and U-100. The term U-40 means that there are 40 units of insulin per milliliter of solution. When measuring the drug in an insulin syringe, one must be careful to use a syringe calibrated to correspond with the strength of the insulin preparation being used. But regardless of the concentration, the action of insulin is basically the same--to enable carbohydrate metabolism to occur and to prevent the accumulation of excess ketone bodies in the blood.
Hypoglycemia and insulin shock result when the level of insulin in the body is too high. This may be the result of an insulin overdose, failure to eat a full meal at the prescribed time, more than the usual amount of exercise, or an emotional or physical upset. Hypoglycemia, if transient and mild, does not cause disabling symptoms; however, if the blood sugar level remains very low for a prolonged period of time, symptoms of cerebral dysfunction or brain damage develop as the brain is deprived of the glucose needed for its normal metabolic activities. Consequently, insulin shock is an ever present danger to those who must take insulin for diabetes mellitus. In addition, devastating retinal, renal and cardiovascular complications are often suffered by diabetics. Recent human and animal studies have indicated that poor control of blood glucose is a principal cause of these complications.
The need exists, therefore, for a device to control the level of blood glucose in a diabetic patient through the infusion of a precise quantity of insulin so that the long-term microvascular and neuropathic complications of diabetes are avoided, or at least minimized. The device must regularly infuse insulin to mimic the release of insulin by the normal pancreas.
Mechanical devices are available to improve the control of blood glucose by the continuous infusion of insulin at a predetermined basal rate. These wearable devices are preprogrammed to infuse shortacting, noncrystalline, regular insulin. Regular insulin should not be confused with the modified long-acting insulins, such a protamine zinc, isophane, globin zinc and lente insulin.
The wearable devices for continuous insulin infusion are also designed to allow the administration of a bolus or increased infusion of regular insulin before each meal. To achieve the desired basal level of insulin, continuous, or at least frequent, activation of the infusion pump is required. Thus, the infusion pump must be carried or worn by the patient. Unfortunately, the currently available wearable infusion devices are expensive, complex and too bulky to be worn comfortably. Moreover, the complicated electronic and mechanical components can wear out or malfunction, and the batteries of the device must be replaced or recharged at regular intervals.
The complexity of these preprogrammed pumps also raises a safety issue. The patient must switch the infusion pump out of the basal infusion mode to activate the pump to infuse each pre-meal insulin bolus. If the patient inadvertently leaves the pump in the bolus infusion mode instead of immediately switching back to basal infusion, the timer may activate frequent bolus infusions which could lead to lifethreatening hypoglycemia or insulin shock. The invention of our copending application Ser. No. 177,892 is directed to the solution of these problems.
In addition, the operation of pressfitting the rod into the piston member can bend the end of the needle which extends into the container. The device of Ser. No. 297,369 includes an annular ledge or indentation along the inner wall of the container to arrest the motion of the piston member on the downward stroke.
Moreover, the needle for infusing the medication should be contoured to permit proper anchoring of the needle to the skin. A straight needle, when secured to the skin by tape or similar fastening means, has a tendency to pivot with the fastening means which serves as a fulcrum thereby widening the needle track; the passage formed between the needle and the tissue of the patient as the needle is inserted into the skin. The device of Ser. No. 297,369 is also directed to the solution of these additional problems.
The present invention relates to the solution of the aforementioned problems and additional difficulties which may arise in the infusion of insulin. According to the present invention, the plunger can be advanced within the container without removing the cap or cover member. Specifically, means is provided for concentrically advancing the plunger comprising a drive tube concentrically mounted about a threaded rod operating within the container, the drive tube having ramp means at the upper end thereof, a ratchet head including a resilient member in operative communication with the upper end of the drive tube and a rotatable knob adjacent the ratchet head whereby rotation of the knob in one direction rotates the drive tube and the threaded rod to deliver the fluid through an outlet of the container.
Because the fluid is delivered only upon rotation of the knob in a predetermined direction, the device can be used without direct viewing--a distinct click is produced upon rotation of the knob when the resilient member of the ratchet head operatively engages the upper end of the drive tube to indicate the delivery of a given volume of fluid.